title: Synthesis and antitumor activity evaluation of a novel series of camptothecin analogs.
abstract: A series of novel 10-substituted camptothecin analogs (3-10) with a carbamate linker were synthesized, and their biological activities were evaluated. The amino acid-linked carbamate derivatives (8-10) of the camptothecin-type natural product not only possessed good to excellent inhibitory activity against three human tumor cell lines K562, HepG2, and HT-29, but also showed significantly less cytotoxicity against normal human cell HEK293 (half maximal inhibiting concentration >10 μM). The selectivity of compound 9 toward tumor cells relative to normal cells is at least 250 times better than that of camptothecin. The preliminary testing result indicated that the solubility of these compounds was also improved compared to that of 10-hydroxy camptothecin.
authors.affiliation: a Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology , Tianjin , 300457 , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lv
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.forename: Shao-Peng
authors.initials: SP
authors.lastname: Wen
authors.forename: Yu-Ou
authors.initials: YO
authors.lastname: Teng
authors.forename: Meng-Xin
authors.initials: MX
authors.lastname: Ma
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002219:Carbamates; D059004:Topoisomerase I Inhibitors; D002166:Camptothecin